Abstract Inflammatory bowel disease entails a complex interaction among intestinal barrier disruption, microbial dysbiosis, and metabolic dysregulation. This research explored the therapeutic potential of citrus-derived exosome-like nanovesicles (CELNs) in dextran sulfate sodium (DSS)-induced murine colitis. The results showed that CELNs (5E+13 particles/kg/day) could effectively mitigate the intestinal inflammatory manifestations and histopathological damage induced by DSS. Additionally, CELNs significantly alleviated colonic oxidative stress and barrier function impairment. Moreover, CELNs remarkably suppressed the TLR4/NF-κB signaling pathway, reduced the secretion of colonic pro-inflammatory cytokines, and attenuated the activation of the NLRP3/caspase-1. Finally, 16S rRNA sequencing and targeted metabolomics indicated that CELNs effectively reshaped the composition of the intestinal microbiota and its derived metabolites (such as short-chain fatty acids, bile acids, indole derivatives, and branched-chain amino acids in feces and serum). These findings demonstrate the unique ability of CELNs to synchronously repair the "barrier-immune-microbiota-metabolite" axis, positioning plant exosomes as novel multitarget therapeutics for colitis.
Zhan et al. (Mon,) studied this question.